The aims of this project are to obtain information from experimental islet transplantation models in rodents which can be applied to the transplantation of islet tissue in humans to reverse insulin dependent diabetes. Three aspects of islet transplantation are to be studied. (1) An investigation of the mechanisms of tolerance which develop in animals carrying cultured allografts and the nature of the antigens that induce this tolerance. This study holds enormous potential for general clinical transplantation in that it may be possible to reduce or eliminate immunosuppression in transplant recipients. (2) A study to investigate the possibility that cell mediated autoimmune attack of islet tissue is restricted by the major histocompatibility complex of the recipient, that is cultured isografts transplanted to spontaneous diabetic animals may be susceptible to autoimmune attack whereas allografts are not. The relationship between the time after onset of disease and the susceptibility of the graft to autoimmune attack will also be investigated. This part of the project has major clinical significance in determining the desirability of matching graft and recipient tissue at the MHC and selecting the optimal time after the onset of disease to transplant islet tissue. (3) To determine the feasibility of using cryopreservation to store fetal proislet tissue. This would allow the development of a bank of donor tissue and would provide the degree of flexibility required if we are to attempt to manipulate the immune system of the recipient prior to transplantation.